近日，首都医科大学北京同仁医院张罗团队研究了Stapokibart治疗严重无法控制的慢性鼻窦炎伴鼻息肉的疗效与安全性。2025年8月18日，《美国医学会杂志》发表了这一成果。

慢性鼻窦炎伴鼻息肉会导致严重的症状和生活质量受损。Stapokibart是一种靶向白细胞介素4Rα的新型单克隆抗体。

为了评估Stapokibart作为鼻内皮质类固醇治疗严重不受控制的慢性鼻窦炎合并鼻息肉患者的疗效和安全性，2022年8月9日至2023年4月28日，研究组进行了一项随机、双盲、三期临床试验，在中国51家医院招募患有慢性鼻窦炎并鼻息肉的成年患者，这些患者有全身皮质类固醇使用史或鼻窦手术史，双侧鼻息肉评分为5分或以上（评分范围为0-8），每周平均鼻塞评分为2分或以上（评分范围为0-3）。嗜酸性慢性鼻窦炎伴鼻息肉定义为血嗜酸性6.9%或更高（无哮喘）或3.7%或更高（有哮喘），或每高倍视场嗜酸性粒细胞计数55或更高，或鼻息肉组织嗜酸性粒细胞计数27%或更高。患者随访于2024年6月25日完成。

干预措施为开始使用糠酸莫米松鼻喷雾剂4周后，每只鼻孔每天100 μg，患者随机接受皮下Stapokibart、300 mg或安慰剂（1:1），每2周一次，连续24周。两组患者均接受Stapokibart治疗28周。共同主要终点是所有患者和嗜酸性粒细胞增多人群在第24周鼻息肉评分（有意义的变化阈值[MCT]≥1分）和鼻塞评分（MCT≥0.5分）较基线的变化。

180例患者中，179例（平均年龄45 [SD， 12.9]岁）；61[34.1%]名妇女)接受了至少1次治疗剂量(Stapokibart组n=90；安慰剂组n = 89)。在总体人群中，stapokibart组和安慰剂组鼻息肉评分从基线到第24周的最小二乘（LS）平均变化分别为2.6和0.3分(LS平均差异为2.3；95% CI, - 2.6 ~ - 1.9)；在嗜酸性粒细胞增多的人群中，变化分别为3.0和0.4个点(LS平均差为2.5；95% CI, - 2.9 ~ - 2.1；)。Stapokibart组与安慰剂组鼻塞评分从基线到第24周的LS平均变化在总体人群中分别为1.2和0.5分(LS平均差异为0.7；95% CI, - 0.9 ~ - 0.5；P < 0.001)和- 1.3 vs - 0.5点(LS平均差异为- 0.8；95% CI, - 1.0 ~ - 0.6)。严重不良事件罕见（stapokibart组为2.2%，安慰剂组为1.1%）。与安慰剂相比，Stapokibart组的关节痛发生率（7.8% vs 0%）和高尿酸血症发生率（5.6% vs 1.1%）分别更高。

研究结果表明，在严重慢性鼻窦炎合并鼻息肉的患者中，每日使用鼻皮质类固醇治疗，在24周时，Stapokibart减少了息肉的大小和鼻症状的严重程度。

附：英文原文

Title: Stapokibart for Severe Uncontrolled Chronic Rhinosinusitis With Nasal Polyps: The CROWNS-2 Randomized Clinical Trial

Author: Shen Shen, Bing Yan, Ming Wang, Di Wu, Yingshi Piao, Jun Tang, Xiangli Yang, Zhiwei Cao, Jinmei Xue, Wen Liu, Shixi Liu, Li Shi, Guangke Wang, Xicheng Song, Yongtian Lu, Jianjun Chen, Luyun Jiang, Jing Ye, Shaoqing Yu, Yucheng Yang, Hongyan Fang, Jiping Li, Haibo Shi, Jiangang Fan, Hongyue Yan, Haifei Wang, Bo Chen, Chengshuo Wang, Luo Zhang, CROWNS- Study Investigators, Lijia Wan, Guolin Tan, Yi Yang, Shiyin Ma, Lizhong Su, Xuezhong Li, Yong Li, Fang Quan, Mingliang Xiang, Yan Jiang, Gang He, Chang Lin, Xiaoyong Ren, Liyan Ni, Xiaoping Gao, Jiusheng Chu, Ruixia Ma, Zhihai Xie, Bing Guan, Shuihong Zhou, Lijian Zhang, Xin Wei, Zhichun Huang, Qingshan Jiang, Xin Wang, Li Zhu, Zian Xiao, Lei Cheng, Kai Wang, Qingqing Yu, Jing Pan, Yuxiao Du, Xiaoqiu Chen, Rui Dong, Shiping Sun, Feng Liu, Shengyang Liu, Pengfei Ba

Issue&Volume: 2025-08-18

Abstract:

Importance  Chronic rhinosinusitis with nasal polyps causes severe symptoms and impaired quality of life. Stapokibart is a novel monoclonal antibody that targets interleukin 4Rα.

Objective  To assess the efficacy and safety of stapokibart as an add-on treatment to intranasal corticosteroids in patients with severe uncontrolled chronic rhinosinusitis with nasal polyps.

Design, Setting, and Participants  From August 9, 2022, to April 28, 2023, this randomized, double-blind, phase 3 clinical trial, conducted at 51 hospitals in China, enrolled adult patients with chronic rhinosinusitis with nasal polyps who had a history of systemic corticosteroid use or sinonasal surgery and a bilateral nasal polyp score of 5 or greater (on a scale of 0-8) and a weekly mean nasal congestion score of 2 or greater (on a scale of 0-3). Eosinophilic chronic rhinosinusitis with nasal polyps was defined as blood eosinophils of 6.9% or greater (without asthma) or 3.7% or greater (with asthma) or an eosinophil count of 55 per high-power field or greater or 27% or greater in nasal polyp tissue. Patient follow-up was completed on June 25, 2024.

Interventions  Four weeks after initiation of mometasone furoate nasal spray, 100 μg in each nostril daily, patients were randomized to receive subcutaneous stapokibart, 300 mg, or placebo (1:1) every 2 weeks for 24 weeks. Both groups then received stapokibart for 28 weeks.

Main Outcomes and Measures  Co–primary end points were changes from baseline in nasal polyp score (meaningful change threshold [MCT] ≥1 point) and nasal congestion score (MCT ≥0.5 points) at week 24 in all patients and in the population with eosinophilia.

Results  Among 180 patients randomized, 179 (mean age, 45 [SD, 12.9] years; 61 [34.1%] women) received at least 1 treatment dose (n=90 for stapokibart; n=89 for placebo). In the overall population, the least-squares (LS) mean change in nasal polyp score from baseline to week 24 in the stapokibart vs placebo groups was 2.6 vs 0.3 points, respectively, (LS mean difference, 2.3; 95% CI, 2.6 to 1.9; P<.001); in the population with eosinophilia, the change was 3.0 vs 0.4 points, respectively (LS mean difference, 2.5; 95% CI, 2.9 to 2.1; P<.001). The LS mean change in nasal congestion score from baseline to week 24 in the stapokibart vs placebo groups was 1.2 vs 0.5 points, respectively, in the overall population (LS mean difference, 0.7; 95% CI, 0.9 to 0.5; P<.001) and 1.3 vs 0.5 points, respectively, in the population with eosinophilia (LS mean difference, 0.8; 95% CI, 1.0 to 0.6; P<.001). Serious adverse events were rare (2.2% in the stapokibart group vs 1.1% in the placebo group). Higher rates of arthralgia (7.8% vs 0%) and hyperuricemia (5.6% vs 1.1%) were reported with stapokibart vs placebo, respectively.

Conclusions and Relevance  Among patients with severe chronic rhinosinusitis with nasal polyps treated with a daily intranasal corticosteroid, stapokibart reduced polyp size and severity of nasal symptoms at 24 weeks.

DOI: 10.1001/jama.2025.12515

Source: https://jamanetwork.com/journals/jama/fullarticle/2837777